Modulation of a 5-Hydroxytryptamine-Related Behaviour by Noradrenaline and Gaba

Abstract

The modulation of 5-hydroxytryptamine (5-HT) mediated head-twitch behaviour by drugs acting at beta-adrenoceptors and at receptor sites related to gamma-aminobutyric acid (GABA) was examined in mice and rats. Both beta,- and betay-adrenoceptor agonists potentiated the Headewicching indu: by a 5-HT precursor in mice and quipazine in rats. The pattern of selective antagonist potency against this effect in mice and the effect of neurotoxin lesions of locus Coeruleus (LC) in rats indicated that the relevant beta)— adrenoceptors are probably located postsynaptically and the betaz-adrenoceptors presynaptically. The potentiating potencies of beta-adrenoceptor agonists on head-twitch response were considerably reduced after 48h withdrawal from chronic but not acute pretreatment of mice with two antidepressants, desmethylimipraimine and iprindole. Results with drugs acting at the GABA and related receptors indicated that GABA, receptors are facilitatory to head-twitch and GABA, receptors are inhibitory and both effects appear to depend on the presence of functional noradrenergic systems probably originating from the LC The relationship between these effects and their implications for understanding the pharmacology of centrally acting drugs is discussed.